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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5203_Библиотеки_им_академика_М_И_Перельмана.pdf
Contributors
xiii
XuefengWang Department of Neurology, The First Afliated Hospital of Chongq-
ing Medical University, Chongqing, China
Yi Wang Department of Neurology, Children’s Hospital of Fudan University,
National Children’s Medical Center, Shanghai, China
YingWang Department of Neurology, The First Afliated Hospital of DaLian
Medical University, DaLian, China
Zan Wang
Department of Neurology, The rst hospital of JIlin University,
Changchun, China
YeWu Department of Pediatrics, Peking University First Hospital, Beijing, China
FeiXiao Department of Neurology, The First Afliated Hospital of Chongqing
Medical University, Chongqing, China
Xin Xu Department of Neurology, The First Afliated Hospital of Chongqing
Medical University, Chongqing, China
ZucaiXu Department of Neurology, Afliated Hospital of Zunyi Medical Univer-
sity, Zunyi, Guizhou, China
ChaoYan Nanjing University, School of Life Sciences, Department of Physiol-
ogy, Nanjing, Jiangsu, China
Yin Yan Epilepsy Rehabilitation center, The Afliated Beibei Hospital of
Chongqing Medical University, Chongqing, China
XiaofengYang Guangzhou National Laboratory, Guangzhou, China
HaiqingZhang Department of Neurology, Afliated Hospital of Zunyi Medical
University, Zunyi, Guizhou, China
Hong Zhang Department of Neurology, Shengjing Hospital of China Medical
University, Shenyang, China
LimingZhang Department of Neurology, The First Afliated Hospital of Harbin
Medical University, Harbin, Heilongjiang, China
LieminZhou Department of Neurology, The Seven Afliated Hospital of Sun Yat-
sen University, Shenzhen, China
Chapter 1
Overview
QunWang, XuefengWang, EmilioPerucca, ZhuoHuang, andXiaofengYang
1.1 Denition ofEpilepsy
The denition of a specic disease is one in which professionals use the simplest
language to summarize the characteristics of the disease to facilitate communication
among peers and more reasonable treatment of the disease. Because of the different
cultures in different countries, it is very difcult to formulate a widely accepted
denition. Understanding of diseases varies across time and across countries.
Therefore, developing a widely accepted denition of disease has become the most
important task of international organizations [1].
Epilepsy is an ancient disease, and there have been descriptions of epilepsy since
the beginning of the written human record, but many people still do not know what
Q. Wang (*)
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University,
Beijing, China
X. Wang
Department of Neurology, The First Afliated Hospital of Chongqing Medical University,
Chongqing, China
E. Perucca
Department of Medicine (Austin Health), The University of Melbourne,
Melbourne, VIC, Australia
Department of Neuroscience, Central Clinical School, Monash University,
Melbourne, VIC, Australia
Z. Huang
State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and
Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University,
Beijing, China
X. Yang
Guangzhou National Laboratory, Guangzhou, China
Ltd. 2025
X. Wang, L. Zhou (eds.), Pharmacological Treatment of Epileptic Seizures,
https://doi.org/10.1007/978-981-96-8520-2_1
1© The Author(s), under exclusive license to Springer Nature Singapore Pte
2
Q. Wang et al.
epilepsy is. People can only see epileptic seizures. Therefore, the understanding of
epilepsy in humans has progressed from the beginning of epileptic seizures, and
epileptic seizures are the basis for people to understand epilepsy [1].
The rst human description of epileptic seizures appeared in 1046BC in the
Babylonian treatise on the diagnosis of disease. Since then, people have gradually paid more attention to this episodic disease. Although clinical manifestations vary from individual to individual, they all have a clear beginning and end.
The duration is also very short. The clinical manifestation is based on the physiological function of the human body, which supports the strengthening of the
physiological function of the human body and does not produce activities outside of those caused by brain function. Each seizure is a temporary disorder of
brain function. The symptoms are almost identical in each episode in the same
individual, indicating that the dysfunction is spread along specic pathologic
pathways [1–4].
Some scholars have summarized the common manifestations of seizures: sudden, transient, stereotypical, and repetitive. The term “paroxysmal” indicates that
the patient’s seizures occur suddenly and end quickly, and the start and end times
are very clear. During the non-seizure period, the patient’s brain function is normal.
Transient refers to the time of each seizure being very short, from a few seconds to
a few minutes, and almost never more than 5minutes according to the guidelines of
the International League against Epilepsy. Stereotypical refers to the fact that
although the clinical manifestations of epilepsy are very rich and diverse, every
seizure in every patient is similar. However, the scope of the spread of epileptic
discharge is different, and its main characteristics must be the same. Repetitive
means that the seizures of epilepsy patients not include only one attack but will be
repeated. Epilepsy is a prominent manifestation of temporary disorders of normal
brain function. Due to the different locations of affected neurons, the range of inuence varies, and patients can experience sensory, motor, autonomic nerve, consciousness, and emotional disorders [2–5].
However, an isolated seizure is not epilepsy, and there are many seizures similar to those caused by epilepsy, including those caused by convulsive syncope,
hyperventilation syndrome, hypertensive encephalopathy, gestational poisoning
in women, hysteria, etc. There are dozens of forms of myoclonus similar to seizures; paroxysmal sleep disorders, such as sleepwalking, night terrors, and periodic tendon movements during sleep, also lead to seizures similar to those of
epilepsy, but they are not epilepsy. Nor does it develop in the same way as epilepsy [1, 4].
The greatest difference between epilepsy and epileptic seizures is that people
with epilepsy have repeated seizures. Some scholars have shown that 50–60% of
patients with similar seizures will not have repeated seizures; therefore, they are not
epileptic, and real epilepsy patients have repeated epileptic seizures. Early epidemiological surveys have also shown that epilepsy patients often relapse within
3years, even if it is an epileptic seizure; before there is a recurrence, the seizure can
only be called a pre-seizure, and the presence of epilepsy can only be considered
after recurrence [1, 4].
1 Overview
3
Epileptic seizures are used to understand epilepsy for humans, and epileptic seizures are the basis of the existence of epilepsy. Epilepsy patients also have characteristics of epileptic seizures, that is, sudden, transient, stereotypic and repetitive
seizures, and their clinical manifestations should also be classied in the category
of brain disorders [1, 4, 5].
In 1870, John Hughlings Jackson proposed a possible mechanism for epileptic
seizures by comparing them with nonepileptic seizures. He suggested that epileptic
seizures were transient brain disorders caused by sudden seizures and transient,
over-synchronous discharge of gray matter neurons. The cause is a sudden release
of energy from neurons. Epilepsy is synonymous with this bursting overexcitation
of gray matter neurons, in what is known as the Jackson hypothesis [1]. In the following century, many studies investigated the mechanisms of seizures. It has been
proposed that epilepsy is a transient disorder of one or several functions of the brain,
originates from the highly synchronized discharge of neurons in the cortex, thalamus, and upper brainstem, and is characterized by highly excited lower neurons
caused by the reduced inhibitory output of the related upper neuron groups to the
lower neuron groups [2–5]. These hypotheses emphasize that electrical and chemical abnormalities in neurons, outside neurons or in the environment are the mechanism of epileptic seizures, greatly enriching the content of the study of epileptic
pathogenesis [2–5].
Based on extensive research, the International League against Epilepsy has proposed a denition of epilepsy, epileptic seizures and epileptic syndromes. “Epilepsy
is a chronic brain disease characterized by epileptic seizures. The highly synchronized abnormal ring of neurons is the root cause of epileptic seizures. Transient
brain dysfunction is the main manifestation of epileptic seizures. Due to the different locations of the affected neurons, the range varies, and due to the differences in
the functions of different brain areas, patients can present with sensory, motor, conscious, emotional, language, behavioral, or autonomic dysfunction.” Epilepsy is
characterized by specic clinical and EEG manifestations, is supported by a specic
etiology, is usually diagnosed as having prognostic and therapeutic signicance, is
accompanied by age-dependent and specic comorbidities, and is called epileptic
syndrome [2–6].
1.2 Classication andDiagnosis ofEpileptic Seizures
The classication and diagnosis of epileptic seizures are extremely important for
clinicians and care teams, patients, and families, and researchers. For patients, the
classication is helpful for clarifying the disease diagnosis and exploring the cause;
for clinicians and care teams, the classication helps to facilitate communication
and discussion. From a research perspective, accurate classication of epileptic seizures facilitates a comprehensive and orderly investigation of the different types of
antiseizure medications and/or surgical treatment modalities, treatment responses,
and the typical clinical course of epileptic seizures.
4
Q. Wang et al.
1.2.1 History ofEpileptic Seizure Classication
The classication of epileptic seizures can be traced back to 1815, when Esquirol
classied epileptic seizures into Grand Mal and Petit Mal according to clinical
severity [7]. In 1937, Gibbs and Lennox etal. classied epileptic seizures into
Grand Mal, Petit Mal, and psychomotor epileptic seizures based on clinical manifestations and EEG features [8]. In 1954, for the rst time, Gastaut, combined
with the study of Peneld etal., established a more systematic classication of
epileptic seizures.
At present, there are two main types of epileptic seizure classication. One is the
electroclinical classication proposed by the International League Against Epilepsy
(ILAE). The other is the seizure symptomatology classication, which is mainly
based on patient clinical symptoms.
In 1964, Gastaut etal. proposed the rst draft of the ILAE classication and
diagnosis of epileptic seizures [9], which was rst revised in 1970 [10]. After
analyzing and summarizing hundreds of video EEG recordings of epileptic seizures [11], the ILAE revised the manuscript in 1981, and BLUME etal. further
standardized the terminology of their descriptions of symptoms during epileptic
seizures in 2001 [12]. It should be noted that the 1981 ILAE classication of epileptic seizures is the most far-reaching classication in the world, and it is still
widely used in clinical practice and scientic research. With the in-depth analysis
of the electroclinical features of an increasing number of epilepsy cases, scholars
have found that some epileptic seizure types cannot be distinguished by the traditional classication of 1981, and the Classication and Nomology Committee of
the ILAE introduced an updated version of the classication in 2010 [13], which
enriched the classication framework. In recent years, rapid advances in related
disciplines such as neuroimaging, genomic technology, and molecular biology
have led to a further increase in the reported types of epileptic seizures, making it
difcult for a broad classication to cover new types of epileptic seizures and
hindering the understanding of the underlying development of the disease and the
complexity of pathological and physiological processes. To adapt to the rapid
development and new understanding in the eld of epilepsy, the ILAE proposed a
new operational classication of epileptic seizures [14] in 2017, which improved
the intuitiveness, transparency, and universality of the classication and proposed
descriptive reporting of seizure types, allowing for the inclusion of previously
unclassiable epileptic seizures.
The symptomatologic classication of epileptic seizures, also known as the
Lüders classication of epileptic seizures, was rst established by Lüders etal. in
1993 from the sole perspective of symptomatology [15] and was revised in 1998
[16] and 2019 [17].
1 Overview
5
1.2.2 Classication ofEpileptic Seizures
1.2.2.1 Classication ofSeizures by theILAE, 1981
The 1981 ILAE classication of epileptic seizures [11] was based on clinical manifestations and electroencephalogram (EEG) features (interictal stage and attack
period), and epileptic seizures are divided into the following:
1. Partial seizure: Initial clinical seizure and EEG features suggest that “a group of
neurons in one cerebral hemisphere are rst involved.” Based on the level of
consciousness, partial seizures can be further divided into simple partial seizures
(SPSs), complex partial seizures (CPSs) and secondarily generalized tonic–
clonic seizures (SGTCs).
2. Generalized seizure: Initial clinical manifestations and EEG features suggest
“simultaneous involvement of both cerebral hemispheres;”
3. Unclassied seizures.
1.2.2.2 Classication ofSeizures by theILAE(2017)
Seizure Classication
The 2017 ILAE classication of seizure type [18] is an operational classication of
seizure types, emphasizing that the specic renement of the classication (basic
version/extended version) can be selected according to clinical needs, and the basic
version (Table1.1) is a reduced form of the extended version (Table1.2). This classication applies to seizures in adults and children but not to seizures in newborns
(neonatal seizures are a separate classication).
It is important to emphasize that the 2017 ILAE classication of seizure types
chart is columnar rather than hierarchical, meaning that levels can be skipped, and
seizure classication may also be terminated at either level. Classication begins
with determining whether the initial manifestations of the seizures are of focal or
generalized onset; if the origin is not observed or obscured, then the seizure should
be of unknown origin. The next level of classication is based on the initial sign or
symptom of a seizure, even if it is not ultimately the most signicant sign or symptom (except behavioral arrest of focal nonmotor onset seizure, because transient
behavioral termination is difcult to determine, so a diagnosis of behavioral arrest
requires behavioral termination to be the primary symptom throughout the seizure).
Focal onset seizures can be classied as “Aware” or “Impaired Awareness,” with
“retained awareness” meaning “aware of self and environment during the seizure,
even if immobile.” Awareness impairment at any time during focal onset seizures
6
Q. Wang et al.
Table 1.1
a
Table 1.2
a
2017 Classication of seizure type, basic version [18]
Focal onset Generalized onset Unknown onset
Aware Impaired awareness Motor Motor
Motor onset Nonmotor (absence) Nonmotor
Nonmotor onset Unclassied
Focal to bilateral tonic–clonic
Due to inadequate information or inability to be placed in other categories
2017 Classication of seizure type, expanded version [18]
Focal onset Generalized onset Unknown onset
Aware Impaired awareness Motor Motor
Motor onset Tonic–clonic Tonic–clonic
Automatisms Clonic Epileptic spasms
Atonic Tonic Nonmotor
Clonic Myoclonic Behavioral arrest
Epileptic spasms Myoclonic–tonic–clonic Unclassied
Hyperkinetic Myoclonic -atonic
Myoclonic Atonic
Tonic Epileptic spasms
Nonmotor onset Nonmotor (absence)
Autonomic Typical
Behavior arrest Atypical
Cognitive Myoclonic
Emotional Eyelid myoclonia
Sensory
Focal to bilateral tonic–clonic
Due to inadequate information or inability to be placed in other categories
a
a
should be classied as focal impaired awareness seizures; if awareness is unknown
during a seizure, the classication of this level (“Aware” or “Impaired Awareness”)
should be ignored when classifying the seizure and go directly to the next level, that
is, the classication of “Motor Onset” or “Nonmotor onset.” In the classication of
motor or nonmotor, motor signals usually dominate unless nonmotor (such as sensory) symptoms and signs are signicant. Therefore, some words can be omitted
without causing ambiguity, such as “focal onset tonic,” rather than “focal motor
onset tonic.”
When classifying generalized onset seizures, “awareness” can be omitted
because awareness impairment is present in most generalized onset seizures.
An episode of “Unknown Onset” is not a truly separate type of seizure but merely
a placeholder for those whose origin is unknown. For example, if a wife is awakened in her sleep and observes her husband’s rst tonic–clonic seizure, the husband’s seizure may be classied as “unknown onset tonic–clonic seizure” in the
initial diagnosis; however, if a seizure with a clear focal onset is subsequently
observed, the husband’s seizure type will be reclassied as “focal to bilateral
1 Overview
7
tonic–clonic.” It is recommended that a seizure be classied as having focal or generalized onset only when there is a high degree of condence (e.g., ≥80%, arbitrarily chosen to parallel the usual allowable beta error) in the accuracy of the
determination; otherwise, the seizure should remain unclassied until more information is available. The term “unclassied seizure” means that the nature of the
origin of the seizure is not specic, there are no motor or nonmotor characteristics,
and the level of awareness is unclear. If any of the above characteristics are known,
a certain classication of the seizure can be made.
The major changes and features of the 2017 classication of seizure type compared to those of the 1981 classication include the following:
1. Focusing on the initial symptoms of the seizure and using them as the main basis
for detailed classication. With either focal onset or generalized onset, seizures
can be roughly divided into motor and nonmotor.
2. The “unknown onset” option was added. Patients with insufcient information
about onset can be temporarily classied into this category, and focal or generalized onset can be determined after the information is complete.
3. In terms of the words used to describe the conscious state of focal-onset seizures,
the more complex word “consciousness” is replaced by the simple and understandable word “awareness” [“aware of self and environment during the
seizure”]. As previously described, “complex partial” can be changed to “focal
impaired awareness.”
4. New types of focal seizures were identied—myoclonic–atonic, clonic, epilep-
tic spasms, tonic, and myoclonic seizures—which were considered to be either
generalized or focal onset seizures. In addition, it also increased the number of
types of seizures that are clinically common or may have locational signicance,
such as automatisms, hyperkinetics, and behavioral arrest.
5. For focal-onset seizures, it is recommended to discard some previously used
terms, such as dyscognitive, simple partial, and psychic.
6. New types of generalized seizures—myoclonus-tonic-clonus, myoclonus-
atonic, epileptic spasm, and myoclonic and eyelid myoclonia seizures.
7. The previous term “secondarily generalized” was replaced by “focal to bilateral
tonic–clonic.”
In summary, the 2017 ILAE classication of seizure types does not represent a
fundamental change but allows for more exibility and transparency in the types
of names.
Common Seizure Types andDiagnostic Points ofthe2017 ILAE Classication
ofSeizure Types
1. Focal onset seizures.
(a) Specication of level of awareness (retained awareness means the person is
aware of the self and the environment during the seizure, even if immobile,
and impaired awareness during any part of the seizure renders it a focal
8
Q. Wang et al.
impaired awareness seizure.) is optional for focal seizures. If awareness is
not applicable or is unknown, it can be simply described as a “focal onset
seizure.”
(b) Automatism refers to the repetitive, aimless, or seemingly purposeful, basi-
cally coordinated involuntary movements or behaviors usually made by
patients with impaired awareness. The common types of automatism include
oropharyngeal automatism, hand automatism, oral automatism and hypermotor automatism.
(c) A hypermotor seizure is a type of focal-onset seizure that mainly involves
the trunk and the proximal extremities of the limb, and the range of movement is usually large, fast, and intense. For example, fast apping movements of the upper limbs or repeated pedaling movements of the lower limbs;
(d) Autonomic seizures refer to focal nonmotor seizures characterized by sig-
nicant changes in autonomic nervous system function. Changes in the
autonomic nervous system may involve cardiopulmonary, papillary, gastrointestinal, perspiratory, vasomotor, and thermoregulatory processes and are
often characterized as tachycardia, hyperventilation, elevated gastric gas,
ushing, pallor, nausea and vomiting, and erect hair.
(e) Focal behavioral arrest seizures are characterized by the cessation of activity
being the dominant feature throughout the seizure and the cessation of activity throughout the entire process;
(f) Cognitive seizures imply impaired language or other cognitive domains or
positive features such as déja vu, hallucinations, illusions, or perceptual
distortions;
(g) Emotional seizures include anxiety, fear, joy, other emotions, or the appear-
ance of affect without subjective emotions;
(h) Sensory seizures refer to self-perceived and experiential seizures induced by
nonexogenous stimuli. Common clinical types include somatosensory,
visual, auditory, olfactory, gustatory, temperature, or vestibular seizures.
(i) Focal to bilateral tonic–clonic seizure is a special seizure type, correspond-
ing to the 1981 phrase “partial onset with secondary generalization.” Focal
to bilateral tonic–clonic seizure reects a propagation pattern of a seizure
rather than a unied seizure type, but it is such a common and important
presentation that the separate categorization was continued.
In general, the EEGs of these focal seizures are characterized by epileptic activity with focal initiation and evolution, which may vary according to the initial site
of discharge, diffusion rate, and extent.
2. Generalized Onset Seizures
(a) Generalized tonic–clonic seizures (GTCSs) are characterized by loss of con-
sciousness and bilateral symmetrical ankylosis followed by clonic movement and are usually accompanied by autonomic nerve involvement. It is the
most obvious form of seizure and used to be called Grand Mal seizure.
(b) Tonic seizures are characterized by continuous contraction and stiffness of
the muscles in the central axis of the body, the proximal ends of both limbs,
1 Overview
9
or the whole body. It usually lasts 2–10seconds and occasionally lasts for a
few minutes. The EEG features during seizures mainly include bilateral
spike rhythm [(20±5Hz)] or low amplitude (10Hz) rhythmic discharge
activity. Tonic seizures are the most important seizure type of Lennox–
Gastaut syndrome (LGS).
(c) Clonic seizures are characterized by bilateral limb rhythmic (1–3Hz) jerks,
with awareness or impaired awareness. During the seizure, the EEG is
mostly generalized spikes/polyspike complexes or spike and slow wave
complexes/polyspikes and slow wave complex synthesis.
(d) Myoclonic seizures are characterized by involuntary, rapid, transient,
electric- like muscle seizures that last from 10–50 milliseconds and rarely
exceed 100 milliseconds. These can involve the whole body or be limited to
certain local muscle or muscle groups. May recur nonrhythmically. The
typical EEG manifestations during seizures include burst generalization
polyspikes and slow wave complexes. Myoclonic seizures, such as those
related to juvenile myoclonic epilepsy (JEM), can be observed in some idiopathic epilepsy patients with a good prognosis. Myoclonic seizures can also
be seen in some cases of epileptic encephalopathy with a poor prognosis and
diffuse brain damage, such as Dravet syndrome and LGS.
(e) Atonic seizures are characterized by a sudden loss or reduction in muscle
tone in the head, trunk, or limbs, with no signicant myoclonus or tonic
components. The seizure lasts approximately 1–2seconds or longer. The
clinical manifestations vary in severity, with mild cases consisting only of
nodding, while severe cases can lead to sudden falls while standing. During
seizures, the EEG shows transient generalization of 2–3Hz spikes and slow
wave complexes/polyspikes and slow wave complexes or sudden voltage
reductions. Atonic seizures are more common in LGS and Doose syndrome
patients.
(f) Myoclonic–tonic–clonic seizures are characterized by single or multiple
clonus or myoclonic jerks of both limbs, which then evolve into tonic–clonic
seizures. This type of seizure is more common in juvenile myoclonic epilepsy (JME) patients.
(g) Myoclonic–atonic seizures are a type of seizure characterized by a myo-
clonic twitch of the limb or trunk followed by hypotonia. These seizures
during orthosis may cause the patient to fall. These seizures were formerly
known as “myoclonic astatic seizures.” This type of seizure is commonly
observed in Doose syndrome patients.
(h) Absence seizures include typical absence, atypical absence, myoclonic
absence, and eyelid myoclonic absence.
Typical Absence Sudden onset and sudden stop of the seizure, manifested by sud-
den cessation of movement or signicant slowing down, with impaired awareness,
with or without mild motor symptoms (such as clonus/myoclonus/rigidity/automatism). The seizure usually lasts 5–20seconds (<30seconds). EEG reveals a 3Hz
(2.5–4Hz) spike and slow wave complex burst with bilateral synchronous symme-